Long term evaluation of proliferative donor antigen-specific reactivity incadaveric kidney transplant recipients

Development of donor-specific proliferative hyporeactivity has been evaluat ed in many studies for its usefulness in identifying transplant recipients at low risk of immunological complications. These studies often result in c ontroversial conclusions, however. The authors claim that the discrepancy i n the predictive value of mixed lymphocyte culture- (MLC) reactivity might partly be due to differences in presentation and interpretation of results. The purpose of this study is to investigate the usefulness of a normalized evaluation of antigen-specific donor-reactivity in a small number of kidne y transplant recipients. This could then serve as a basis for an extended c linical study. Ten cadaveric kidney recipients were tested for proliferativ e reactivity to donor- and third-party antigens up to 20 months posttranspl antation. Expressing donor-specific reactivity as a relation between the pe rcentage of pretransplant responses towards donor splenocytes and the perce ntage of pretransplant responses towards third-party donor cells should min imize influences of e.g, uremia, current immunosuppression or infections on the evaluation of specific reactivity and thus should allow an evaluation of the donor-specificity of T-cell alloresponses independently of fluctuati ons in global responsiveness. Four of ten recipients acquired a state of do nor-specific hyporeactivity (<75% relative specific reactivity) at 20 month s posttransplantation (61 +/- 12%, mean +/- SD). Six patients were classifi ed non-hyporeactive (98 +/- 10% mean relative specific reactivity). Relativ e specific reactivity did not correlate with the levels of general reactivi ty. Three of the four hyporeactive and four of the six non-hyporeactive pat ients developed acute rejection. Stable graft function at 20 months posttra nsplantation (serum creatinine less than or equal to 2 mg/dl) was not close ly related to the reactivity status, as five of eight patients with well-fu nctioning grafts did not develop relative specific hyporeactivity. One reci pient with chronic rejection was classified hyporeactive. One non-hyporeact ive patient lost his graft due to non-immunological causes. Our data sugges t that posttransplant relative specific reactivity does not predict acute r ejection. Downregulation of donor-specific reactivity might not be a prereq uisite for stable graft function but could help identifying recipients who require less immunosuppression. This, however, remains to be established in a prospective immunosuppression-weaning study.